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Increased tight junction permeability: a possible mechanism of oestrogen cholestasis
Author(s) -
ELIAS ELWYN,
IQBAL SAJIDA,
KNUTTON STUART,
HICKEY ANTHONY,
COLEMAN ROGER
Publication year - 1983
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1983.tb00118.x
Subject(s) - medicine , endocrinology , cholestasis , chemistry , diethylstilbestrol , paracellular transport , phenolphthalein , bilirubin , tight junction , estrogen , permeability (electromagnetism) , biochemistry , membrane
. Ethinyl oestradiol increased rat biliary permeability for 3 H‐inulin and 14 C‐sucrose, and significantly raised serum concentrations of bile acids after 3 and 7 days' treatment ( P < 0.0005) and bilirubin after 7 days ( P < 0.005) but not after 3 days. Following intravenous infusion of bromsulphthalein or phenolphthalein, ethinyl oestradiol‐treated rats had elevated plasma concentrations of the three bile constituents, bromsulphthalein ( P < 0.0005 after 3 and 7 days), bromsulphthalein‐glutathione conjugate ( P < 0.005 after 3 days; P 0.0005 after 7 days) and phenolphthalein glucuronide ( P < 0.005 after 3 days; P < 0.0005 after 7 days), but the plasma concentration of unconjugated phenolphthalein, which was undetectable in bile, was unchanged. Similar changes followed partial biliary obstruction produced by bile cannula elevation. This pattern suggests that biliary constituents are refluxing from bile to plasma via the paracellular pathway, a concept further supported by structural changes in tight junction morphology in the oestrogen‐treated rats. ‘Leakiness’ of canalicular tight junctions may explain the pathophysiology of oestrogen‐induced cholestasis.